Evaluation of liposomal clodronate in experimental spontaneous autoimmune hemolytic anemia in dogs

Mathes, Mark; Jordan, Michael B.; Dow, Steven

doi:10.1016/j.exphem.2006.05.014

Cited by 19 publications

(17 citation statements)

References 41 publications

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“…Clodronate liposomes (CLs) were prepared as described previously and used within a week of preparation (21). Control PBS liposomes (PLs) were prepared according to the same protocol used for CLs, but liposomes were rehydrated in a molar-equivalent concentration of PBS instead of clodronate.…”

Section: Methodsmentioning

confidence: 99%

Critical Protective Role for MCP-1 in Pneumonic Burkholderia mallei Infection

Goodyear¹,

Jones²,

Troyer³

et al. 2009

The Journal of Immunology

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Burkholderia mallei is a Gram-negative bacterial pathogen of domestic equidae and humans that can cause severe, rapidly life-threatening pneumonic infections. Little is known regarding the role of chemokines and early cellular immune responses in protective immunity to pulmonary infection with B. mallei. Although the role of MCP-1 in Gram-positive bacterial infections has been previously investigated, the role of MCP-1 in immunity to acute pneumonia caused by Gram-negative bacteria, such as B. mallei, has not been assessed. In a mouse model of pneumonic B. mallei infection, we found that both MCP-1−/− mice and CCR2−/− mice were extremely susceptible to pulmonary infection with B. mallei, compared with wild-type (WT) C57Bl/6 mice. Bacterial burden and organ lesions were significantly increased in CCR2−/− mice, compared with WT animals, following B. mallei challenge. Monocyte and dendritic cell recruitment into the lungs of CCR2−/− mice was significantly reduced in comparison with that in WT mice following B. mallei infection, whereas neutrophil recruitment was actually increased. Depletion of monocytes and macrophages prior to infection also greatly raised the susceptibility of WT mice to infection. Production of IL-12 and IFN-γ in the lungs after B. mallei infection was significantly impaired in both MCP-1−/− and CCR2−/− mice, whereas treatment of CCR2−/− mice with rIFN-γ restored protection against lethal challenge with B. mallei. Thus, we conclude that MCP-1 plays a key role in regulating cellular immunity and IFN-γ production following pneumonic infection with B. mallei and therefore may also figure importantly in other Gram-negative pneumonias.

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Section: Methodsmentioning

confidence: 99%

Critical Protective Role for MCP-1 in Pneumonic Burkholderia mallei Infection

Goodyear¹,

Jones²,

Troyer³

et al. 2009

The Journal of Immunology

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“…The uptake of LC by myeloid cells results in the delivery of clodronate (dichloromethylene diphosphonate) into the cytoplasm, where it competes for ATP binding and induces cell death via apoptosis 2 , 3 , 6 - 8 …”

Section: Introductionmentioning

confidence: 99%

Depletion of phagocytic myeloid cells triggers spontaneous T cell- and NK cell-dependent antitumor activity

Guth

Hafeman²,

Dow

2012

OncoImmunology

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Depletion of tumor associated macrophages and inhibition of tumor angiogenesis have been invoked as the principle mechanisms underlying the antitumor activity of liposomal clodronate (LC). However, previous studies have not examined the effects of LC on systemic antitumor immunity. Here, we used mouse tumor models to elucidate the role of T and NK cells in the antitumor activity elicited by the systemic administration of LC. Strikingly, we found that the antitumor activity of LC is completely abolished in immunodeficient Rag1−/− mice. Moreover, both Cd4−/− and Cd8−/− mice as well as mice depleted of NK cells manifested a significant impaired ability to control tumor growth following LC administration. Treatment with LC did not result in an overall increase in T- or NK-cell numbers in tumors or lymphoid organs, nor was tumor infiltration with T or NK cells altered. However, T and NK cells isolated from the spleen of LC-treated mice exhibited significant increased tumor-specific secretion of interferon γ and interleukin 17 and greater cytolytic activity. We concluded that the antitumor effects of LC are largely dependent on the generation of systemic T-cell and NK- cell activity, most likely owing to the depletion of immune suppressive myeloid cell populations in lymphoid tissues. These findings suggest that the systemic administration of LC may constitute an effective means for non-specifically augmenting the antitumor activity of T and NK cells.

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“…There is no evidence that heparin is effective, even though it is commonly used as adjunct therapy (Mathes et al 2006;Whelan et al 2009). It may be difficult to establish the dose of heparin to be used because of differences in the pharmacokinetics of heparin in healthy and diseased dogs (Breuhl et al 2009).…”

Section: Anticoagulationmentioning

confidence: 99%

“…Splenectomy has been investigated in two small retrospective cohort studies of dogs with IMHA (Feldman et al 1985;Horgan et al 2009), but because the dogs also received medical treatment and blood transfusions and neither study included a control group, definite conclusions could not be drawn about Notes: The factors that were associated with increased (") or decreased (#) mortality risk are summarized in this the efficacy of splenectomy in IMHA. Liposomal clodronate improved survival in dogs with IMHA compared with that of a historical control group matched for disease severity (Mathes et al 2006). …”

Section: Immunomodulationmentioning

confidence: 99%

Canine idiopathic immune-mediated haemolytic anaemia: a review with recommendations for future research

Piek

2011

Veterinary Quarterly

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Evaluation of liposomal clodronate in experimental spontaneous autoimmune hemolytic anemia in dogs

Cited by 19 publications

References 41 publications

Critical Protective Role for MCP-1 in Pneumonic Burkholderia mallei Infection

Critical Protective Role for MCP-1 in Pneumonic Burkholderia mallei Infection

Depletion of phagocytic myeloid cells triggers spontaneous T cell- and NK cell-dependent antitumor activity

Canine idiopathic immune-mediated haemolytic anaemia: a review with recommendations for future research

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